This project is a study of the metabolism of normal and injured dog myocardium. The metabolic changes occurring in injured cells are correlated with the ultrastructural changes found in the same tissue. Both reversible and irreversible forms of injury are under study. The reversible forms of injury are induced by anoxia, acute left ventricular failure, and brief periods of ischemia, and autolysis. The irreversible form is induced in the posterior papillary muscle of the dog by high ligation of the circumflex branch of the left coronary artery. Ths aim is to establish the changes occurring during the early phase of ischemic injury with especial attention to discovering those changes which dictate the onset of irreversibility. Also under study are structural functional interrelationships in mitochondria isolated from damaged tissue or damaged by in vitro autolysis. Studies of regionalization of blood flow in areas of acute ischemic injury as well as factors which may modify distribution of arterial flow also are in progress.